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The optimal immune checkpoint inhibitors combined with chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis

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Abstract

Background

Immune checkpoint inhibitors (ICIs) plus chemotherapy (CT) have strikingly expanded the therapeutic landscape for advanced non-small cell lung cancer (NSCLC), but little is known about which is superior. We performed a meta-analysis that compared the efficacy and safety of PD-1 inhibitor + CT with PD-L1 inhibitor + CT.

Methods

PubMed, Embase, Web of Science, Cochrane Library, and major international scientific meetings were searched for relevant randomized controlled trials (RCTs), and the indirect analysis was performed for PD-1 + CT vs PD-L1 + CT. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (TRAEs).

Results

8 phase III RCTs with 4253 patients comparing PD-1/PD-L1 + CT in NSCLC were included. The PD-1 + CT led to notably longer OS most in low/negative expression of PD-L1 for NSCLC patients compared with PD-L1 + CT. In terms of Grade 3–5 TRAEs, the results showed that PD-1 + CT and PD-L1 + CT exclusively increased the risk of adverse incidence than CT alone, especially for PD-L1 + CT (p < 0.00001). For subgroups including female, young patients, patients with nonsmoker, and EGFR/ALK wild-type, PD-1 + CT was associated with prolonged OS (p < 0.05). Meanwhile, for no liver metastasis of NSCLC patients, we found obviously OS advantage for patients treated with PD-1 + CT compared to PD-L1 + CT.

Conclusions

ICIs + CT seemed to be more effective first-line regimen and PD-1 + CT could be recommended as the first-rank therapy for advanced NSCLC patients with low/negative expression of PD-L1. However, we should be particularly vigilant about the occurrence of the Grade 3–5 TRAEs.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81372436), and Science and Technology Open Cooperation Project of Henan Province (182106000062).

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  1. Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Dong Ming Road 127#, Zhengzhou, 450008, China

    Y. Yang, H. Luo, X. L. Zheng & H. Ge

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Correspondence to H. Ge.

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12094_2020_2502_MOESM1_ESM.tif

Figure S1 Forest plots of hazard ratios comparing OS between patients treated with PD-1 + CT or PD-L1 + CT according to PD-L1 expression. PD-1: anti-PD-1 inhibitors combined with chemotherapy; PD-L1: anti-PD-L1 inhibitors combined with chemotherapy; *PD-L1 high (TC3 or IC3). Low PD-L1 expression: PDL1 1-49% or TC1/2 (TC ≥1% and <50%) or IC1/2 (IC ≥1% and <10%). High PD-L1 expression: PD-L1 ≥ 50% or TC3 (TC≥50%) or IC3 (IC≥10%). TC: tumor cells. IC: tumor-infiltrating immune cells. (TIF 23054 kb)

12094_2020_2502_MOESM2_ESM.tif

Figure S2 Forest plots of hazard ratios comparing PFS between patients treated with PD-1 + CT or PD-L1 + CT according to PD-L1 expression. PD-1: anti-PD-1 inhibitors combined with chemotherapy; PD-L1: anti-PD-L1 inhibitors combined with chemotherapy; *PD-L1 high (TC3 or IC3). Low PD-L1 expression: PDL1 1-49% or TC1/2 (TC ≥1% and <50%) or IC1/2 (IC ≥1% and <10%). High PD-L1 expression: PD-L1 ≥ 50% or TC3 (TC≥50%) or IC3 (IC≥10%). TC: tumor cells. IC: tumor-infiltrating immune cells (TIF 23852 kb)

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Yang, Y., Luo, H., Zheng, X.L. et al. The optimal immune checkpoint inhibitors combined with chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis. Clin Transl Oncol 23, 1117–1127 (2021). https://doi.org/10.1007/s12094-020-02502-8

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